In the proposed studies, we hope to better understand the role of "mineralocorticoid" steroids in hypertension. To do this we plan to determine the extent to which substances present in plasma can inhibit the binding of 3H-aldosterone by the kidney mineralocorticoid receptors. This competitor activity will be taken as one index of mineralocorticoid activity. Plasma from a number of types of hypertension, particularily low-renin hypertension will be examined, and the competitor activity determined will be compared with that expected from the measured aldosterone, deoxycorticosterone (DOC) and cortisol. In cases where excess competitor activity are found (one such patient has thus far been identified), the radioreceptor assay will be used to help with isolation of the putative novel steroid(s). The receptors will also be used to better determine the factors involved in the initial steroid-receptor interaction. The results may be useful for predicting the proposed (based on positive preliminary results) to determine whether there can be mineralocorticoid receptor-mediated effects on vascular endothelium and pituitary in an effort to know whether these tissues can be targets for direct mineralcorticoid responses that might possibly affect the blood pressure. We hope also to examine the complexity of the mineralocorticoid response and the effects of these steroids on certain gene products (lysyl oxidase) that may affect the blood pressure. Finally, we hope to look for rapid effects of mineralocorticoids on chromatin structure as a possible new type of bioassay for mineralocorticoid hormone action. It is hoped that these studies can help to better delineate the extent to which steroids with mineralocorticoid activity can be in excess in various hypertension syndromes; subclassify low-renin hypertension; understand the requirements for mineralocorticoid action; and determine whether certain extrarenal tissues can be targets for mineralocorticoids in hypertension.